aging

Question 1

average life expectancy

Answer 1

80 yrs. 77yrs for men, 82 yrs for women

Question 2

What is the expected maximum life expectancy

Answer 2

85-90 yrs

Question 3

define life span and the human life span

Answer 3

maximal life expectancy- for humans it is 110yrs but very few individuals reach this age

Question 4

Normal Effects of Aging

Answer 4

•From the late twenties to ninety, there is a steady decline in the function of nearly every body system.

Question 5

effects of aging on the brain

Answer 5

atrophy, 10% loss of volume between age 35 and 60 as indicated from brain scan data. Mainly due to loss of myelin. Some loss of subcortical nuclei in the gray matter. Often mild problems with cognition, memory

Question 6

Effects of aging on lung

Answer 6

loss of elastic tissue. Accumulation of anthracotic pigment (especially for city dwellers), often very mild emphysematous changes

Question 7

aging of hematopoietic system

Answer 7

•atrophy of spleen, thymus and bone marrow.

Question 8

aging of soft tissue

Answer 8

increase in body fat

Question 9

aging of kidneys

Answer 9

loss of nephrons

Question 10

aging of heart and liver

Answer 10

accumulation of lipofuscin, the so-called “wear and tear” pigment- a product of the peroxidation of unsaturated fatty acids.

Question 11

aging of blood vessels

Answer 11

Generalized atherosclerosis, varicosities are common

Question 12

diseases associated with aging

Answer 12

1. cancer- most deaths occur around age 70. carcinoma is dz of advanding age. 2. atherosclerosis. 3. Strokes. 4.diabetes- non insulin dependent. 5. thromboembolism. 6. Parkinsons and Alzheimers.

Question 13

theories of aging

Answer 13

1. the clock theory- the aging process and death are programmed in the same way that early development is programmed. Aging is controlled by aging genes.. 2. the rust theory- aging results from the accumulation over time of oxidative damage to cells and tissues

Question 14

Evidence for the clock theory

Answer 14

1. Somatic cells are “programmed” to die after they have undergone a set number of cell divisions. Fibroblasts from old adults may senesce after only 10 to 20 doublings (compared to 80 doublings in fetus). 2. there are human genetic conditions that cause premature aging. 3. longevity runs in families. 4. genes that affect life span have been identified in some animals

Question 15

What causes somatic cells to senesce

Answer 15

Telomeres which help stabilize chromosome ends and are needed for faithful chromosome segregation are shortened each cell division.

Question 16

Telomerase complex

Answer 16

Catalytically adds TTAGGG to 3’ end of telomere of the leading strand

Question 17

telomerase diseases

Answer 17

1. aplastic anemia- mutation in telomerase reverse transcriptase. 2. bone marrow failure- mutations in TERC. 3. Dyskeratosis congenta- skin hyperpigmentation, oral leukoplakia, dystrophic nails—bone marrow failure, pul/liver fibrosis are all due to mutations in Dyskerin

Question 18

Progeria

Answer 18

Mutation in Lamin A gene. rare, affected individuals age at an accelerated rate, life span is only agout 10 years. Death usually from cardiac or cerebrovascular disease.

Question 19

function of Lamin A gene/protein

Answer 19

Lamin A is an intermediate filament present in the nucleus. It forms part of the apparatus that tethers the chromosome to the nuclear envelope.

Question 20

Werners syndrome

Answer 20

affected patients show signs of aging in their early twenties- develop cataracts, aging changes in skin and hair. Early onset of cancer and heart disease- death by age 50. Mutation is in the gene for DNA helicase- defect in repair of DNA damage

Question 21

Mutations that increase longevity in C. elegans (nematodes)

Answer 21

1.Age-1 gene- mutation inactivates a phosphatidylinositol 3-kinase 2. Insulin-like growth factor receptor gene mutations. 3. Clk -1 gene– encodes an enzyme that helps synthesize coenzyme Q, a component of the mitochondrial respiratory chain. 4. Sir2– encodes a histone deacetylase that promotes gene “silencing”. Overproduction increases longevity. Stabilizers rDNA genes in nucleolus.

Question 22

Evidence for oxidation theory of aging

Answer 22

1. lipofuscin, cross linked collagen and oxidized DNA/ protein build up. 2. Restricting calories (and lowering metabolic rate) increases longevity by 30-50%. 3. increased somatic mutations in mitochondrial DNA

Question 23

What causes mutations in mitochondrial DNA to build up over time?

Answer 23

MtDNA sustains a high rate of oxidative injury because of its location and from the fact that it can not be repaired very well. The accumulation of mutations in MtDNA in somatic tissues may be what causes the well documented decline in oxidative phosphorylation that occurs as we age.

Question 24

List the molecules that favor aging when activated

Answer 24

GH, IGF-1, (growth pathways) P13K, Akt, mTOR (nutrition sensing)

Question 25

List the molecules with anti-aging properties

Answer 25

FOXO, PTEN, AMPK, Sirt1, PGC-1a. Inhibition of mTOR is antiaging and mimics caloric restriction

Question 26

rapamycin

Answer 26

inhibits mTOR, extending lifespan